What is juvenile myelomonocytic leukemia? Juvenile myelomonocytic leukemia, also known as JMML, is a malignant blood cell disorder of infancy and early childhood, characterized by enlarged liver and spleen due to abnormal excessive growth of a type of blood cells called myeloid precursor cells.

What are signs of JMML? Typical signs of JMML include: pallor (appearing pale), fever, infection, skin bleeding, and cough. Most children with JMML have an enlarged spleen and liver, which can lead to a distended abdomen. Many patients also have big lymph nodes. Some children show severe weight loss. Skin rashes are common.

What is the natural course of JMML? JMML in most children is fatal if left untreated. There are some specific genetic lesions for which the disease spontaneously resolves without stem cell transplant. The median survival time without stem cell transplantation for all JMML children is about one year (meaning half of patients live about this long).

Which diseases can mimic JMML? Signs and symptoms of some infections can look like JMML, specifically Epstein Barr virus, cytomegalovirus, and other viral infections. In addition, disorders of blood cell function, such as leukocyte adhesion deficiency and some metabolic disorders, can give rise to a clinical and hematologic picture resembling JMML. Therefore, the diagnosis of JMML needs to be carefully established by experienced physicians.

How frequent is JMML? Epidemiological studies from Denmark and British Columbia show a JMML incidence of 1.2 cases per million children per year. A lower incidence of 0.6 cases per million children per year has been reported in the United Kingdom. JMML predominates in infants and toddlers. Boys are affected more often than girls.

What is the connection between Neurofibromatosis type 1 and JMML? The association between neurofibromatosis type 1 (NF1) and JMML has long been established. A clinical diagnosis of NF1 is made in approximately 15% of patients with JMML. The risk of developing JMML for patients with NF1 is 200- 350-fold higher than in patients without NF1 (from Stiller et al. 1994 Br J Cancer. Vol. 70: pp. 969-972).

What is the association between JMML and Noonan syndrome? In rare cases, infants with Noonan Syndrome develop a JMML-like disorder. Noonan syndrome is characterized by distinct facial features, growth retardation, and heart anomalies. Notably, the JMML-like disorder in patients with Noonan syndrome often resolves without aggressive treatment.

Is it possible to develop the JMML-like disorder with Noonan syndrome after one year of age? Usually, infants with Noonan syndrome are diagnosed with the JMML-like disorder in early infancy.

What is the role of mutations of RAS and PTPN11 in JMML? A number of gene mutations are known to be involved in the development of JMML. RAS mutations are observed in approximately 25% of JMML cases while another 35% of patients harbor the PTPN11 mutation. It remains largely unknown why some children acquire these genetic defects associated with JMML. In a small minority of children with JMML, the mutations are inherited from the parents.

Can patients with JMML be cured? Currently, only hematopoietic stem cell transplantation from another person (sometimes a sibling, oftentimes someone outside of the family) offers the possibility of long-term cure. Donor search should be initiated soon after the diagnosis because data suggest that young age at transplantation is associated with improved survival.

Can patients with relapsed JMML be cured? Patients who relapsed with JMML have a chance to be cured with a second hematopoietic stem cell transplantation (see Yoshimi 2007 Leukemia Vol. 21, pp. 556–560).